PEGylated Polymeric Nanoparticles Loaded with 2-Methoxyestradiol for the Treatment of Uterine Leiomyoma in a Patient-Derived Xenograft Mouse Model

Enazy, Sanaalarab Al; Kirschen, Gregory W.; Vincent, Kathleen L.; Yang, Jinping; Saada, Jamal I.; Shah, Mansi; Oberhauser, Andrés F.; Bujalowski, Paul J.; Salama, Salama A.; Kılıç, Gökhan; Rytting, Erik; Borahay, Mostafa A.

doi:10.1016/j.xphs.2023.07.018

Cited by 5 publications

(8 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Intracellularly, when estrogen activates ER⍺, the MAPK and PI3K/Akt pathways become activated, stimulating proliferation and inhibiting apoptosis in uterine smooth muscle cells [ 52 ]. We recently found that PEGylated polymeric nanoparticles loaded with 2-methoxyestradiol, injected intraperitoneally in a patient-derived xenograft fibroid mouse model, led to a significant shrinkage of fibroids after one month of treatment [ 56 ]. In this study, we found that the viability of human uterine leiomyoma (HuLM) cells was diminished in a dose-dependent fashion, with the lowest viability at 10 μM, and an in vivo volume of human fibroid tissue markedly diminished in the 2-ME group compared to control after 28 days of treatment.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Obesity Contributes to Transformation of Myometrial Stem-Cell Niche to Leiomyoma via Inducing Oxidative Stress, DNA Damage, Proliferation, and Extracellular Matrix Deposition

Afrin

Kirschen

Borahay

2023

Genes

Self Cite

View full text Add to dashboard Cite

Leiomyomas (fibroids) are monoclonal tumors in which myometrial stem cells (MSCs) turn tumorigenic after mutation, abnormal methylation, or aberrant signaling. Several factors contribute to metabolic dysfunction in obesity, including abnormal cellular proliferation, oxidative stress, and DNA damage. The present study aims to determine how adipocytes and adipocyte-secreted factors affect changes in MSCs in a manner that promotes the growth of uterine leiomyomas. Myometrial stem cells were isolated from the uteri of patients by fluorescence-activated cell sorting (FACS) using CD44/Stro1 antibodies. Enzyme-linked immunosorbent assay (ELISA), Western blot, and immunocytochemistry assays were performed on human adipocytes (SW872) co-cultured with MSCs and treated with leptin or adiponectin to examine the effects of proliferation, extracellular matrix (ECM) deposition, oxidative damage, and DNA damage. Co-culture with SW872 increased MSC proliferation compared to MSC culture alone, according to 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) results. The expressions of PCNA and COL1A increased significantly with SW872 co-culture. In addition, the expression of these markers was increased after leptin treatment and decreased after adiponectin treatment in MSCs. The Wnt/β-catenin and TGF-β/SMAD signaling pathways promote proliferation and ECM deposition in uterine leiomyomas. The expression of Wnt4, β-catenin, TGFβ3, and pSMAD2/3 of MSCs was increased when co-cultured with adipocytes. We found that the co-culture of MSCs with adipocytes resulted in increased NOX4 expression, reactive oxygen species production, and γ-H2AX expression. Leptin acts by binding to its receptor (LEP-R), leading to signal transduction, resulting in the transcription of genes involved in cellular proliferation, angiogenesis, and glycolysis. In MSCs, co-culture with adipocytes increased the expression of LEP-R, pSTAT3/STAT3, and pERK1/2/ERK/12. Based on the above results, we suggest that obesity may mediate MSC initiation of tumorigenesis, resulting in leiomyomas.

show abstract

Section: Discussionmentioning

confidence: 99%

“…The estradiol-dependent progesterone receptor regulation we observed in fibroid cells suggests that circulating estrogen levels directly impact fibroid signaling, leading to proliferation versus quiescence or apoptosis [ 56 ]. Progesterone receptor levels have also been linked to adipogenesis and obesity progression [ 61 ].…”

Section: Discussionmentioning

confidence: 99%

Obesity Contributes to Transformation of Myometrial Stem-Cell Niche to Leiomyoma via Inducing Oxidative Stress, DNA Damage, Proliferation, and Extracellular Matrix Deposition

Afrin

Kirschen

Borahay

2023

Genes

Self Cite

View full text Add to dashboard Cite

show abstract

“…Through adjustments in the nanomaterials' size, surface modifications, and release mechanisms, their accumulation and drug delivery efficiency at the lesion site can be enhanced while minimizing adverse effects on healthy tissues. For example, in the treatment of uterine fibroids, drugs encapsulated within biologically active nanomaterials can be released at the specific lesion site through precise targeting mechanisms, enabling localized treatment [ 95 , 96 ]. Additionally, biologically active nanomaterials can be employed in thermotherapy utilizing magnetic hyperthermia, where an externally applied magnetic field generates heat, leading to thermal ablation of the lesions [ 97 ].…”

Section: Application Of Nanotechnology In the Treatment Of Female Rep...mentioning

confidence: 99%

The utilization of nanotechnology in the female reproductive system and related disorders

Luo,

Jia,

Xing

et al. 2024

Heliyon

View full text Add to dashboard Cite

“…Previous studies have found that 2-ME, an anti-tumor agent, inhibits cell proliferation and collagen biosynthesis in human and rat UL cell lines [64,65]. However, the use of 2-ME as a therapeutic agent has been hindered by low solubility and bioavailability [9]. Recent research has focused on the use of 2-ME nanoparticles in patient-derived UL tissue xenografts [9,23].…”

Section: Liposomal 2-methoxyestradiol (2-me) Therapymentioning

confidence: 99%

“…Though nanoparticles have mostly been studied to treat cancer, the recent literature reveals they have efficacy in the treatment of other diseases. Nanomedicine-based approaches have also been applied to benign gynecologic disorders such as uterine leiomyoma, endometriosis, polycystic ovarian syndrome (PCOS), and menopause [9][10][11][12] (Figure 1). Although there are established treatment algorithms for these gynecologic conditions, there is still a need for more innovative treatment options to improve the quality of life of patients.…”

Section: Introductionmentioning

confidence: 99%

The Role of Nanomedicine in Benign Gynecologic Disorders

Lulseged,

Ramaiyer,

Michel

et al. 2024

Molecules

Self Cite

View full text Add to dashboard Cite

Nanomedicine has revolutionized drug delivery in the last two decades. Nanoparticles appear to be a promising drug delivery platform in the treatment of various gynecological disorders including uterine leiomyoma, endometriosis, polycystic ovarian syndrome (PCOS), and menopause. Nanoparticles are tiny (mean size < 1000 nm), biodegradable, biocompatible, non-toxic, safe, and relatively inexpensive materials commonly used in imaging and the drug delivery of various therapeutics, such as chemotherapeutics, small molecule inhibitors, immune mediators, protein peptides and non-coding RNA. We performed a literature review of published studies to examine the role of nanoparticles in treating uterine leiomyoma, endometriosis, PCOS, and menopause. In uterine leiomyoma, nanoparticles containing 2-methoxyestradiole and simvastatin, promising uterine fibroid treatments, have been effective in significantly inhibiting tumor growth compared to controls in in vivo mouse models with patient-derived leiomyoma xenografts. Nanoparticles have also shown efficacy in delivering magnetic hyperthermia to ablate endometriotic tissue. Moreover, nanoparticles can be used to deliver hormones and have shown efficacy as a mechanism for transdermal hormone replacement therapy in individuals with menopause. In this review, we aim to summarize research findings and report the efficacy of nanoparticles and nanotherapeutics in the treatment of various benign gynecologic conditions.

show abstract

PEGylated Polymeric Nanoparticles Loaded with 2-Methoxyestradiol for the Treatment of Uterine Leiomyoma in a Patient-Derived Xenograft Mouse Model

Cited by 5 publications

References 45 publications

Obesity Contributes to Transformation of Myometrial Stem-Cell Niche to Leiomyoma via Inducing Oxidative Stress, DNA Damage, Proliferation, and Extracellular Matrix Deposition

Obesity Contributes to Transformation of Myometrial Stem-Cell Niche to Leiomyoma via Inducing Oxidative Stress, DNA Damage, Proliferation, and Extracellular Matrix Deposition

The utilization of nanotechnology in the female reproductive system and related disorders

The Role of Nanomedicine in Benign Gynecologic Disorders

Contact Info

Product

Resources

About